{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:48:36Z","timestamp":1792039716462,"version":"4.4.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"the China National Key Research & Development (R&D) Plan"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1038\/s41591-026-04585-2","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T09:02:10Z","timestamp":1786093330000},"page":"3842-3852","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Large-scale whole-genome sequencing reveals the landscape and health implications of de novo mutations"],"prefix":"10.1038","volume":"32","author":[{"given":"Na","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3909-5671","authenticated-orcid":false,"given":"Juncheng","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6624-1742","authenticated-orcid":false,"given":"Hong","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangqian","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5717-9385","authenticated-orcid":false,"given":"Jiangbo","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianfeng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingmin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0557-865X","authenticated-orcid":false,"given":"Congcong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziye","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ci","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayun","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumei","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8961-8971","authenticated-orcid":false,"given":"Yuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingxia","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufeng","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9821-6955","authenticated-orcid":false,"given":"Hongxia","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0249-5337","authenticated-orcid":false,"given":"Guangfu","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8193-9276","authenticated-orcid":false,"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2581-5906","authenticated-orcid":false,"given":"Hongbing","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8277-5234","authenticated-orcid":false,"given":"Zhibin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"4585_CR1","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/ng.646","volume":"42","author":"SB Ng","year":"2010","unstructured":"Ng, S. B. et al. Exome sequencing identifies MLL2mutations as a cause of Kabuki syndrome. Nat. Genet. 42, 790\u2013793 (2010).","journal-title":"Nat. Genet."},{"key":"4585_CR2","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/nrg3241","volume":"13","author":"JA Veltman","year":"2012","unstructured":"Veltman, J. A. & Brunner, H. G. De novo mutations in human genetic disease. Nat. Rev. Genet. 13, 565\u2013575 (2012).","journal-title":"Nat. Rev. Genet."},{"key":"4585_CR3","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1016\/j.tig.2019.08.005","volume":"35","author":"JM Goldmann","year":"2019","unstructured":"Goldmann, J. M., Veltman, J. A. & Gilissen, C. De novo mutations reflect development and aging of the human germline. Trends Genet. 35, 828\u2013839 (2019).","journal-title":"Trends Genet."},{"key":"4585_CR4","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nature24018","volume":"549","author":"H Jonsson","year":"2017","unstructured":"Jonsson, H. et al. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. Nature 549, 519\u2013522 (2017).","journal-title":"Nature"},{"key":"4585_CR5","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/35049558","volume":"1","author":"JF Crow","year":"2000","unstructured":"Crow, J. F. The origins, patterns and implications of human spontaneous mutation. Nat. Rev. Genet. 1, 40\u201347 (2000).","journal-title":"Nat. Rev. Genet."},{"key":"4585_CR6","doi-asserted-by":"crossref","unstructured":"Genome of the Netherlands Consortium.Whole-genome sequence variation, population structure and demographic history of the Dutch population. Nat. Genet. 46, 818\u2013825 (2014).","DOI":"10.1038\/ng.3021"},{"key":"4585_CR7","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/nature11396","volume":"488","author":"A Kong","year":"2012","unstructured":"Kong, A. et al. Rate of de novo mutations and the importance of father\u2019s age to disease risk. Nature 488, 471\u2013475 (2012).","journal-title":"Nature"},{"key":"4585_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10486","volume":"7","author":"WS Wong","year":"2016","unstructured":"Wong, W. S. et al. New observations on maternal age effect on germline de novo mutations. Nat. Commun. 7, 10486 (2016).","journal-title":"Nat. Commun."},{"key":"4585_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-59750-x","volume":"16","author":"OI Garcia-Salinas","year":"2025","unstructured":"Garcia-Salinas, O. I. et al. The impact of ancestral, genetic, and environmental influences on germline de novo mutation rates and spectra. Nat. Commun. 16, 4527 (2025).","journal-title":"Nat. Commun."},{"key":"4585_CR10","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoaf006","volume":"2025","author":"W Xiong","year":"2025","unstructured":"Xiong, W., Tang, X., Han, L. & Ling, L. Paternal age and neonatal outcomes: a population-based cohort study. Hum. Reprod. Open 2025, hoaf006 (2025).","journal-title":"Hum. Reprod. Open"},{"key":"4585_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000040","volume":"6","author":"S Saha","year":"2009","unstructured":"Saha, S. et al. Advanced paternal age is associated with impaired neurocognitive outcomes during infancy and childhood. PLoS Med. 6, e40 (2009).","journal-title":"PLoS Med."},{"key":"4585_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1146\/annurev-genet-112618-043617","volume":"54","author":"RJ Aitken","year":"2020","unstructured":"Aitken, R. J., De Iuliis, G. N. & Nixon, B. The sins of our forefathers: paternal impacts on de novo mutation rate and development. Annu. Rev. Genet. 54, 1\u201324 (2020).","journal-title":"Annu. Rev. Genet."},{"key":"4585_CR13","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1038\/s41422-021-00521-w","volume":"31","author":"C Wang","year":"2021","unstructured":"Wang, C. et al. Association of assisted reproductive technology, germline de novo mutations and congenital heart defects in a prospective birth cohort study. Cell Res. 31, 919\u2013928 (2021).","journal-title":"Cell Res."},{"key":"4585_CR14","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn7113","volume":"380","author":"NB Rockweiler","year":"2023","unstructured":"Rockweiler, N. B. et al. The origins and functional effects of postzygotic mutations throughout the human life span. Science 380, eabn7113 (2023).","journal-title":"Science"},{"key":"4585_CR15","doi-asserted-by":"crossref","unstructured":"Sasani, T. A. et al. Large, three-generation human families reveal post-zygotic mosaicism and variability in germline mutation accumulation. Elife 8, e46922 (2019).","DOI":"10.7554\/eLife.46922"},{"key":"4585_CR16","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.ajhg.2015.05.008","volume":"97","author":"R Acuna-Hidalgo","year":"2015","unstructured":"Acuna-Hidalgo, R. et al. Post-zygotic point mutations are an underrecognized source of de novo genomic variation. Am. J. Hum. Genet. 97, 67\u201374 (2015).","journal-title":"Am. J. Hum. Genet."},{"key":"4585_CR17","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1126\/science.aan8690","volume":"359","author":"T Bae","year":"2018","unstructured":"Bae, T. et al. Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis. Science 359, 550\u2013555 (2018).","journal-title":"Science"},{"key":"4585_CR18","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1016\/j.cell.2012.11.019","volume":"151","author":"JJ Michaelson","year":"2012","unstructured":"Michaelson, J. J. et al. Whole-genome sequencing in autism identifies hot spots for de novo germline mutation. Cell 151, 1431\u20131442 (2012).","journal-title":"Cell"},{"key":"4585_CR19","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.gpb.2021.09.005","volume":"20","author":"Y Hong","year":"2022","unstructured":"Hong, Y. et al. Common postzygotic mutational signatures in healthy adult tissues related to embryonic hypoxia. Genomics Proteomics Bioinformatics 20, 177\u2013191 (2022).","journal-title":"Genomics Proteomics Bioinformatics"},{"key":"4585_CR20","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1038\/ng.3597","volume":"48","author":"JM Goldmann","year":"2016","unstructured":"Goldmann, J. M. et al. Parent-of-origin-specific signatures of de novo mutations. Nat. Genet. 48, 935\u2013939 (2016).","journal-title":"Nat. Genet."},{"key":"4585_CR21","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17, 405\u2013424 (2015).","journal-title":"Genet. Med."},{"key":"4585_CR22","unstructured":"Durkie, M. et al. ACGS best practice guidelines for variant classification in rare disease 2024. https:\/\/www.genomicseducation.hee.nhs.uk\/wp-content\/uploads\/2024\/08\/ACGS-2024_UK-practice-guidelines-for-variant-classification.pdf (Association for Clinical Genomic Science, 2024)."},{"key":"4585_CR23","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/ng1939","volume":"39","author":"M Tartaglia","year":"2007","unstructured":"Tartaglia, M. et al. Gain-of-function SOS1mutations cause a distinctive form of Noonan syndrome. Nat. Genet. 39, 75\u201379 (2007).","journal-title":"Nat. Genet."},{"key":"4585_CR24","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s10038-005-0239-7","volume":"50","author":"T Niihori","year":"2005","unstructured":"Niihori, T. et al. Functional analysis of PTPN11\/SHP-2 mutants identified in Noonan syndrome and childhood leukemia. J. Hum. Genet. 50, 192\u2013202 (2005).","journal-title":"J. Hum. Genet."},{"key":"4585_CR25","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s004310051018","volume":"158","author":"G Corsello","year":"1999","unstructured":"Corsello, G. et al. Maternal phenylketonuria in two Sicilian families identified by maternal blood phenylalanine level screening and identification of a new phenylalanine hydroxylase gene mutation (P407L). Eur. J. Pediatr. 158, 83\u201384 (1999).","journal-title":"Eur. J. Pediatr."},{"key":"4585_CR26","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1146\/annurev-genom-031714-125740","volume":"15","author":"L Segurel","year":"2014","unstructured":"Segurel, L., Wyman, M. J. & Przeworski, M. Determinants of mutation rate variation in the human germline. Annu. Rev. Genomics Hum. Genet. 15, 47\u201370 (2014).","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"4585_CR27","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1038\/s41586-024-08450-5","volume":"639","author":"G Palsson","year":"2025","unstructured":"Palsson, G. et al. Complete human recombination maps. Nature 639, 700\u2013707 (2025).","journal-title":"Nature"},{"key":"4585_CR28","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1038\/ng.2702","volume":"45","author":"SA Roberts","year":"2013","unstructured":"Roberts, S. A. et al. An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat. Genet. 45, 970\u2013976 (2013).","journal-title":"Nat. Genet."},{"key":"4585_CR29","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/s41586-022-04972-y","volume":"607","author":"M Petljak","year":"2022","unstructured":"Petljak, M. et al. Mechanisms of APOBEC3 mutagenesis in human cancer cells. Nature 607, 799\u2013807 (2022).","journal-title":"Nature"},{"key":"4585_CR30","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/0168-9525(93)90089-Z","volume":"9","author":"AP Grollman","year":"1993","unstructured":"Grollman, A. P. & Moriya, M. Mutagenesis by 8-oxoguanine: an enemy within. Trends Genet. 9, 246\u2013249 (1993).","journal-title":"Trends Genet."},{"key":"4585_CR31","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","volume":"578","author":"LB Alexandrov","year":"2020","unstructured":"Alexandrov, L. B. et al. The repertoire of mutational signatures in human cancer. Nature 578, 94\u2013101 (2020).","journal-title":"Nature"},{"key":"4585_CR32","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.ajhg.2011.12.017","volume":"90","author":"A Goriely","year":"2012","unstructured":"Goriely, A. & Wilkie, A. O. Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease. Am. J. Hum. Genet. 90, 175\u2013200 (2012).","journal-title":"Am. J. Hum. Genet."},{"key":"4585_CR33","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1038\/ng.3577","volume":"48","author":"J Gratten","year":"2016","unstructured":"Gratten, J. et al. Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations. Nat. Genet. 48, 718\u2013724 (2016).","journal-title":"Nat. Genet."},{"key":"4585_CR34","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.puhe.2014.03.010","volume":"128","author":"MJ Platt","year":"2014","unstructured":"Platt, M. J. Outcomes in preterm infants. Public Health 128, 399\u2013403 (2014).","journal-title":"Public Health"},{"key":"4585_CR35","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/s41586-025-09579-7","volume":"647","author":"V Seplyarskiy","year":"2025","unstructured":"Seplyarskiy, V. et al. Hotspots of human mutation point to clonal expansions in spermatogonia. Nature 647, 429\u2013435 (2025).","journal-title":"Nature"},{"key":"4585_CR36","doi-asserted-by":"publisher","first-page":"2645","DOI":"10.1093\/humrep\/deae230","volume":"39","author":"RJ Aitken","year":"2024","unstructured":"Aitken, R. J. Paternal age, de novo mutations, and offspring health? New directions for an ageing problem. Hum. Reprod. 39, 2645\u20132654 (2024).","journal-title":"Hum. Reprod."},{"key":"4585_CR37","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1038\/287560a0","volume":"287","author":"BK Duncan","year":"1980","unstructured":"Duncan, B. K. & Miller, J. H. Mutagenic deamination of cytosine residues in DNA. Nature 287, 560\u2013561 (1980).","journal-title":"Nature"},{"key":"4585_CR38","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.fertnstert.2025.02.009","volume":"124","author":"GD Adamson","year":"2025","unstructured":"Adamson, G. D. et al. How many infants have been born with the help of assisted reproductive technology? Fertil. Steril. 124, 40\u201350 (2025).","journal-title":"Fertil. Steril."},{"key":"4585_CR39","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1093\/humrep\/dey118","volume":"33","author":"Z Li","year":"2018","unstructured":"Li, Z. et al. ICSI does not increase the cumulative live birth rate in non-male factor infertility. Hum. Reprod. 33, 1322\u20131330 (2018).","journal-title":"Hum. Reprod."},{"key":"4585_CR40","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/s41586-025-09448-3","volume":"647","author":"MDC Neville","year":"2025","unstructured":"Neville, M. D. C. et al. Sperm sequencing reveals extensive positive selection in the male germline. Nature 647, 421\u2013428 (2025).","journal-title":"Nature"},{"key":"4585_CR41","doi-asserted-by":"publisher","first-page":"2454","DOI":"10.1073\/pnas.1521325113","volume":"113","author":"GJ Maher","year":"2016","unstructured":"Maher, G. J. et al. Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes. Proc. Natl Acad. Sci. USA 113, 2454\u20132459 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4585_CR42","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1093\/humupd\/dmr004","volume":"17","author":"HG Al-Inany","year":"2011","unstructured":"Al-Inany, H. G. et al. GnRH antagonists are safer than agonists: an update of a Cochrane review. Hum. Reprod. Update 17, 435 (2011).","journal-title":"Hum. Reprod. Update"},{"key":"4585_CR43","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1093\/humupd\/dmx017","volume":"23","author":"CB Lambalk","year":"2017","unstructured":"Lambalk, C. B. et al. GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type. Hum. Reprod. Update 23, 560\u2013579 (2017).","journal-title":"Hum. Reprod. Update"},{"key":"4585_CR44","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1016\/S0140-6736(01)06797-6","volume":"358","author":"JA Huirne","year":"2001","unstructured":"Huirne, J. A. & Lambalk, C. B. Gonadotropin-releasing-hormone-receptor antagonists. Lancet 358, 1793\u20131803 (2001).","journal-title":"Lancet"},{"key":"4585_CR45","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1016\/S1472-6483(10)61059-0","volume":"14","author":"HG Al-Inany","year":"2007","unstructured":"Al-Inany, H. G., Abou-Setta, A. M. & Aboulghar, M. Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane review. Reprod. Biomed. Online 14, 640\u2013649 (2007).","journal-title":"Reprod. Biomed. Online"},{"key":"4585_CR46","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1093\/humrep\/17.4.874","volume":"17","author":"H Al-Inany","year":"2002","unstructured":"Al-Inany, H. & Aboulghar, M. GnRH antagonist in assisted reproduction: a Cochrane review. Hum. Reprod. 17, 874\u2013885 (2002).","journal-title":"Hum. Reprod."},{"key":"4585_CR47","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1095\/biolreprod59.3.661","volume":"59","author":"F Raga","year":"1998","unstructured":"Raga, F. et al. Quantitative gonadotropin-releasing hormone gene expression and immunohistochemical localization in human endometrium throughout the menstrual cycle. Biol. Reprod. 59, 661\u2013669 (1998).","journal-title":"Biol. Reprod."},{"key":"4585_CR48","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1093\/molehr\/4.9.893","volume":"4","author":"KW Dong","year":"1998","unstructured":"Dong, K. W. et al. Expression of gonadotropin-releasing hormone (GnRH) gene in human uterine endometrial tissue. Mol. Hum. Reprod. 4, 893\u2013898 (1998).","journal-title":"Mol. Hum. Reprod."},{"key":"4585_CR49","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.fertnstert.2005.12.020","volume":"86","author":"S Shen","year":"2006","unstructured":"Shen, S. et al. Day 2 transfer improves pregnancy outcome in in vitro fertilization cycles with few available embryos. Fertil. Steril. 86, 44\u201350 (2006).","journal-title":"Fertil. Steril."},{"key":"4585_CR50","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.fertnstert.2006.02.088","volume":"86","author":"A Agarwal","year":"2006","unstructured":"Agarwal, A., Said, T. M., Bedaiwy, M. A., Banerjee, J. & Alvarez, J. G. Oxidative stress in an assisted reproductive techniques setting. Fertil. Steril. 86, 503\u2013512 (2006).","journal-title":"Fertil. Steril."},{"key":"4585_CR51","doi-asserted-by":"publisher","first-page":"e354","DOI":"10.1093\/ije\/dyad139","volume":"52","author":"J Du","year":"2023","unstructured":"Du, J. et al. Cohort profile: the Jiangsu Birth Cohort. Int. J. Epidemiol. 52, e354\u2013e363 (2023).","journal-title":"Int. J. Epidemiol."},{"key":"4585_CR52","doi-asserted-by":"publisher","first-page":"14110","DOI":"10.1021\/acs.est.4c01945","volume":"58","author":"H Lv","year":"2024","unstructured":"Lv, H. et al. Prenatal parental exposure to metals and birth defects: a prospective birth cohort study. Environ. Sci. Technol. 58, 14110\u201314120 (2024).","journal-title":"Environ. Sci. Technol."},{"key":"4585_CR53","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114\u20132120 (2014).","journal-title":"Bioinformatics"},{"key":"4585_CR54","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows\u2212Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009).","journal-title":"Bioinformatics"},{"key":"4585_CR55","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.1093\/bioinformatics\/btu314","volume":"30","author":"GG Faust","year":"2014","unstructured":"Faust, G. G. & Hall, I. M. SAMBLASTER: fast duplicate marking and structural variant read extraction. Bioinformatics 30, 2503\u20132505 (2014).","journal-title":"Bioinformatics"},{"key":"4585_CR56","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1101\/gr.246934.118","volume":"30","author":"F Zhang","year":"2020","unstructured":"Zhang, F. et al. Ancestry-agnostic estimation of DNA sample contamination from sequence reads. Genome Res. 30, 185\u2013194 (2020).","journal-title":"Genome Res."},{"key":"4585_CR57","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297\u20131303 (2010).","journal-title":"Genome Res."},{"key":"4585_CR58","doi-asserted-by":"publisher","first-page":"2867","DOI":"10.1093\/bioinformatics\/btq559","volume":"26","author":"A Manichaikul","year":"2010","unstructured":"Manichaikul, A. et al. Robust relationship inference in genome-wide association studies. Bioinformatics 26, 2867\u20132873 (2010).","journal-title":"Bioinformatics"},{"key":"4585_CR59","unstructured":"Feurer, M. et al. Efficient and robust automated machine learning. In Proc. 28th International Conference on Neural Information Processing Systems - Volume 2 (eds Cortes, C., Lee, D. D., Sugiyama, M. & Garnett, R.) 2755\u20132763 (MIT Press, 2015); https:\/\/dl.acm.org\/doi\/10.5555\/2969442.2969547"},{"key":"4585_CR60","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/s41587-019-0074-6","volume":"37","author":"JM Zook","year":"2019","unstructured":"Zook, J. M. et al. An open resource for accurately benchmarking small variant and reference calls. Nat. Biotechnol. 37, 561\u2013566 (2019).","journal-title":"Nat. Biotechnol."},{"key":"4585_CR61","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00746-1","volume":"12","author":"F Muyas","year":"2020","unstructured":"Muyas, F., Zapata, L., Guigo, R. & Ossowski, S. The rate and spectrum of mosaic mutations during embryogenesis revealed by RNA sequencing of 49 tissues. Genome Med. 12, 49 (2020).","journal-title":"Genome Med."},{"key":"4585_CR62","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.ajhg.2017.05.013","volume":"101","author":"R Acuna-Hidalgo","year":"2017","unstructured":"Acuna-Hidalgo, R. et al. Ultra-sensitive sequencing identifies high prevalence of clonal hematopoiesis-associated mutations throughout adult life. Am. J. Hum. Genet. 101, 50\u201364 (2017).","journal-title":"Am. J. Hum. Genet."},{"key":"4585_CR63","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/s41588-018-0071-6","volume":"50","author":"JM Goldmann","year":"2018","unstructured":"Goldmann, J. M. et al. Germline de novo mutation clusters arise during oocyte aging in genomic regions with high double-strand-break incidence. Nat. Genet. 50, 487\u2013492 (2018).","journal-title":"Nat. Genet."},{"key":"4585_CR64","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1089\/cmb.2014.0157","volume":"22","author":"M Patterson","year":"2015","unstructured":"Patterson, M. et al. WhatsHap: weighted haplotype assembly for future-generation sequencing reads. J. Comput. Biol. 22, 498\u2013509 (2015).","journal-title":"J. Comput. Biol."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04585-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04585-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04585-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:31:27Z","timestamp":1792038687000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04585-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":64,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["4585"],"URL":"https:\/\/doi.org\/10.1038\/s41591-026-04585-2","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"assertion":[{"value":"19 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}